The goals of this research are to use high-resolution maps of regional lung mechanical properties to detect and follow the progression of lung disease. Pulmonary disease processes, including emphysema, interstitial fibrosis, cancer, pulmonary embolism, acute lung injury and more, alter the material properties of lung tissue and change the mechanics of the respiratory system. Furthermore, while these mechanical changes (and the disease process itself) originate at a local level, they are largely asymptomatic and invisible to currently available global measures of lung function such as pulmonary function tests until they have significantly advanced. We will use image registration to construct a high-resolution 3D map of the regional distribution of lung tissue specific volume change (related to specific compliance) and the lung tissue strain tensor between multiple respiratory-gated volumetric images of the breathing lung. The computational tools to be developed in this project will provide the ability to assess local volume, grayscale, and shape changes for arbitrary regions of interest in the lung parenchyma across the respiratory cycle. We expect that, by tracking the 3D distribution of regional lung specific volume change and the magnitude and direction of lung strain, we can examine the effects that localized pathological processes have on diseased tissue as well as surrounding normal tissue. Such information may provide new insights regarding pulmonary pathophysiology in, for instance, the proliferation of lung destruction in emphysema, the ventilation and perfusion mismatches in pulmonary emboli episodes, the effect of regional airway closure in asthma, and the regional mechanics of acute lung injury and the propagation of ventilator-associated lung injury. This information is now critical to the development and evaluation of new pulmonary disease therapies.